Taxol, or paclitaxel as it is sometimes called, has been investigated as an anti-cancer agent. Taxol is a plant product derived in minute quantities from the needles and bark of the western pacific yew, Taxus brevifolia. In chemotherapy, taxol is known as an anti-microtubule agent and is thought to inhibit cell mitosis through the enhancement of the rate of microtubular assembly and prevention of microtubular depolymerization. Numerous studies indicate that the agent has activity against several malignancies. To date, its use has been severely limited by, among other things, its short supply, poor water solubility and immunogenicity.
The pacific yew is a rare, slow-growing tree which is not typically cultivated. In addition, the anti-neoplastic portions of the tree are very minute. Extraction of these portions is complicated and costly. One solution to the problem of short supply has been suggested in U.S. Pat. No. 5,019,504 which discloses an artificial media for producing certain desirable alkaloids. Alternatively, synthetic derivations such as taxotere and taxol intermediates have also been reported. See, for example, U.S. Pat. No. 5,015,744.
Hypersensitivity reactions from taxol administration are known. See, for example, J. Clin. Oncol. 8:1263-1268 (1990). Indeed, since taxoids are usually extracted from a natural plant source, some hypersensitivity is expected. Moreover, certain non-aqueous vehicles which have been used to overcome the water solubility problems of taxol have also been implicated in causing hypersensitivity reactions.
Although taxoids hold promise as therapeutic agents, there is a need to provide taxoid-based derivatives which are more water soluble and/or are more active against a wider range of virulent neoplasms than taxol.